Effect of insulin insufficiency on ultrastructure and function in skeletal muscle
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB65585 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR11939232.fastq.gz | Fastqsanger.gz | |||
| ERR11939233.fastq.gz | Fastqsanger.gz | |||
| ERR11939234.fastq.gz | Fastqsanger.gz | |||
| ERR11939235.fastq.gz | Fastqsanger.gz | |||
| ERR11939236.fastq.gz | Fastqsanger.gz |
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Project description:Decreased insulin availability and high blood glucose levels, the hallmark features of poorly controlled diabetes, drive disease progression and are associated with decreased skeletal muscle mass. We have shown that mice with -cell dysfunction and normal insulin sensitivity have decreased skeletal muscle mass. This project asks how insulin deficiency impacts on the structure and function of the remaining skeletal muscle in these animals. Methods: Skeletal muscle function was determined by measuring exercise capacity and specific muscle strength prior to and after insulin supplementation for 28 days in 12-week-old mice with conditional -cell deletion of the ATP binding cassette transporters ABCA1 and ABCG1 (β-DKO mice). Abca1 and Abcg1 floxed (fl/fl) mice were used as controls. RNAseq was used to quantify changes in transcripts in soleus and extensor digitorum longus muscles. Skeletal muscle and mitochondrial morphology were assessed by transmission electron microscopy. Myofibrillar Ca2+ sensitivity and maximum isometric single muscle fibre force were assessed using MyoRobot biomechatronics technology. Results: RNA transcripts were significantly altered in β-DKO mice compared to fl/fl controls (32 in extensor digitorum longus and 412 in soleus). Exercise capacity and muscle strength were significantly decreased in β-DKO mice compared to fl/fl controls (p = 0.012), and a loss of structural integrity was also observed in skeletal muscle from the β-DKO mice. Supplementation of β-DKO mice with insulin restored muscle integrity, strength and expression of 13 and 16 of the dysregulated transcripts in and extensor digitorum longus and soleus muscles, respectively. Conclusions: Insulin insufficiency due to -cell dysfunction perturbs the structure and function of skeletal muscle. These adverse effects are rectified by insulin supplementation.
2023-09-26 | E-MTAB-13315 | biostudies-arrayexpress
Project description:Obesity-related insulin resistance (OIR) is one of the main contributors to type 2 diabetes and other metabolic diseases. Protein kinases are implicated in key signaling steps including insulin signaling and glucose metabolism. Molecular mechanisms underlying OIR involving global active kinases remain less understood. Herein, we report findings from an in vivo active kinase profiling study in skeletal muscle from lean control (Lean) and OIR human participants, which identified the 1st active kinome comprised of 54 active protein kinases in human skeletal muscle. The activities of 23 kinases were different in OIR compared to Lean muscle (11 hyper- and 12 hypo-active), while their protein abundance was the same between the two groups. The activities of multiple kinases involved in AMPK and p38 signaling were lower in OIR compared to Lean. On the contrary, multiple kinases in JNK signaling pathway exhibited higher activity in OIR vs. Lean muscle. The kinase-substrate-prediction based on experimental data further confirmed a potential down-regulation of insulin signaling (e.g., inhibited phosphorylation of insulin receptor substrate-1 and AKT1/2). These findings provide a global view of the active kinome in OIR and Lean muscle, pinpoint novel specific impairment in kinase activities in multiple signaling pathways important for skeletal muscle insulin resistance, and provide potential drug targets (i.e., abnormal active kinase) to prevent and/or reverse skeletal muscle insulin resistance in humans.
2020-01-23 | PXD011909 | Pride
Project description:Insulin resistance, the defective regulation of glucose metabolism by insulin, increases the risk of type 2 diabetes and cardiovascular disease. It is not yet known how insulin resistance remodels signalling networks in human tissues. Here, we define the signalling architecture of insulin resistance in skeletal muscle. We measured phenotypes and phosphoproteomes of insulin resistant and insulin sensitive subjects as they responded to exercise and an insulin infusion, quantifying more than 26,000 phosphosites in 114 skeletal muscle biopsies. Incorporating a temporal component to personalised phosphoproteomics identified signalling linked with the range of insulin sensitivity across the participants.
2024-11-22 | PXD032948 | Pride
Project description:Insulin action in target tissues involved precise regulation of gene expression. To define the set of insulin-regulated genes in human skeletal muscle, we analyzed the global changes in mRNA levels during a 3-h hyperinsulinemic euglycemic clamp in vastus lateralis muscle of six healthy subjects. Using 29,308 cDNA element microarrays, we found that the mRNA expression of 762 genes, including 353 expressed sequence tags, was significantly modified during insulin infusion. 478 were up-regulated and 284 down-regulated. Most of the genes with known function are novel targets of insulin. They are involved in the transcriptional and translational regulation (29%), intermediary and energy metabolisms (14%), intracellular signaling (12%), and cytoskeleton and vesicle traffic (9%). Other categories consisted of genes coding for receptors, carriers, and transporters (8%), components of the ubiquitin/proteasome pathways (7%) and elements of the immune response (5.5%). These results thus define a transcriptional signature of insulin action in human skeletal muscle. They will help to better define the mechanisms involved in the reduction of insulin effectiveness in pathologies such as type 2 diabetes mellitus, a disease characterized by defective regulation of gene expression in response to insulin. An all pairs experiment design type is where all labeled extracts are compared to every other labeled extract. Using regression correlation
2005-12-20 | E-GEOD-3881 | biostudies-arrayexpress
Project description:The current study aimed to address the hypothesis that programmed expression of key miRNAs in skeletal muscle mediates the development of insulin resistance, and consequently long-term health. We thus examined microRNA signatures in skeletal muscle of programmed insulin resistant rats offspring from high fat-fed dams vs control offspring from chow fed dams. Skeletal muscle (soleus) was collected from the hind limb of 1 year old male offspring (6 from control dams, 6 from high fat-fed dams) . Ramaciotti Centre for Genomics (UNSW, sydney, Australia)
2015-04-25 | E-GEOD-68225 | biostudies-arrayexpress
Project description:The current study aimed to address the hypothesis that programmed expression of key miRNAs in skeletal muscle mediates the development of insulin resistance, and consequently long-term health. We thus examined microRNA signatures in skeletal muscle of programmed insulin resistant rats offspring from high fat-fed dams vs control offspring from chow fed dams.
2015-04-25 | GSE68225 | GEO
Project description:The aim of this study was therefore to investigate molecular mechanisms associated with insulin sensitivity in skeletal muscle by relating global skeletal muscle gene expression with a surrogate measure of insulin sensitivity, i.e. homeostatic model assessment of insulin resistance (HOMA-IR). To identify genes with skeletal muscle expression related to insulin sensitivity, we obtained muscle biopsies from 38 non-diabetic participants in study A. We then profiled muscle gene expression using Affymetrix oligonucleotide microarrays (Affymetrix Custom Array NuGO-Hs1a520180 GeneChip). To replicate the findings from study A, we included 9 non-diabetic participants from study B. We performed skeletal muscle gene expression profiling from these participants using the Agilent oligonucleotide microarrays (Agilent-G4112F (Feature Number version)). Insulin sensitivity was estimated using the 1/HOMA-IR method calculated from the oral glucose tolerance test (OGTT) values. This SuperSeries is composed of the SubSeries listed below.
2020-11-19 | GSE161721 | GEO
Project description:Insulin action in target tissues involved precise regulation of gene expression. To define the set of insulin-regulated genes in human skeletal muscle, we analyzed the global changes in mRNA levels during a 3-h hyperinsulinemic euglycemic clamp in vastus lateralis muscle of six healthy subjects. Using 29,308 cDNA element microarrays, we found that the mRNA expression of 762 genes, including 353 expressed sequence tags, was significantly modified during insulin infusion. 478 were up-regulated and 284 down-regulated. Most of the genes with known function are novel targets of insulin. They are involved in the transcriptional and translational regulation (29%), intermediary and energy metabolisms (14%), intracellular signaling (12%), and cytoskeleton and vesicle traffic (9%). Other categories consisted of genes coding for receptors, carriers, and transporters (8%), components of the ubiquitin/proteasome pathways (7%) and elements of the immune response (5.5%). These results thus define a transcriptional signature of insulin action in human skeletal muscle. They will help to better define the mechanisms involved in the reduction of insulin effectiveness in pathologies such as type 2 diabetes mellitus, a disease characterized by defective regulation of gene expression in response to insulin. An all pairs experiment design type is where all labeled extracts are compared to every other labeled extract. Keywords: all_pairs
2005-12-21 | GSE3881 | GEO
Project description:Mitochondrial H+-ATP synthase in human skeletal muscle: contribution to dyslipidemia and insulin resistance
2017-05-30 | MSV000081125 | MassIVE
Project description:To identify insulin responsive genes in humans, in the first protocol, skeletal muscle biopsies from six non-diabetic subjects were obtained before and after a two-hour of hyperinsulinaemic (infusion rate 40 mU/m2/min) euglycemic clamp. A variable infusion of glucose (180 g/l) enriched with tritiated glucose (100 μCi/500 ml) maintained euglycemia during insulin infusion, with monitoring of plasma glucose concentration every 5 to 10 min during the basal and clamp periods using an automated glucose oxidation method (Glucose Analyzer 2, Beckman Instruments, Fullerton, CA). In the second protocol, skeletal muscle biopsies from six non-diabetic subjects were obtained before and after a 3-hour hyperinsulinemic (infusion rate 40 mU/m2/min) euglycemic clamp in order to increase the effects of insulin on gene expression. A variable infusion of glucose (180 g/l) was used to maintain euglycemia during insulin infusion with monitoring of plasma glucose concentration every 5 to 10 min using an automated glucose oxidation method (Glucose Analyzer 2, Beckman Instruments, Fullerton, CA). Keywords: dose response The muscle biopsies were obtained from the vastus lateralis muscle under local anesthesia before and after hyperinsulinaemic (infusion rate 40 mU/m2/min) euglycemic clamp
2007-03-01 | E-GEOD-7146 | biostudies-arrayexpress